Background Compressed sensing (CS) has been widely used to improve the speed of MRI, but the feasibility of application in 3D intracranial MR angiography (MRA) needs to be evaluated in clinical practice. Purpose To evaluate the clinical feasibility of CS‐MRA in comparison with conventional 3D‐MRA (Con‐MRA). Study Type Retrospective. Subjects Forty‐nine consecutive patients with suspected intracranial arterial disease. Field Strength/Sequence 3T MRI. 3D time‐of‐flight (TOF) MRA using a CS algorithm and conventional 3D TOF MRA scan. Assessment Three radiologists (4, 11, and 12 years of experience in neuroradiology) independently assessed the image quality, vascular lesions, and variations of intracranial arteries of both CS‐MRA and Con‐MRA, respectively. Statistical Tests The Kendall W test was performed to assess the interobserver agreement of image quality and intracranial arterial stenosis. A nonparametric test (Wilcoxon test) was used for comparison of the image quality and definition of the external carotid artery (ECA). Weighted kappa analysis was performed for the interstudy agreement of intracranial arterial stenosis. The aneurysm, decreased branches, congenital hypoplasia, absence, and variant branching of intracranial arteries were observed and evaluated for interobserver agreement and interstudy agreement by kappa analysis. Paired‐t‐tests for signal‐to‐noise ratio (SNR) and contrast‐to‐noise ratio (CNR) were conducted. Results Image quality is better for CS‐MRA compared with Con‐MRA with significance (Z = –3.710 to –2.673, with P < 0.01). The interstudy agreement of lesion and variation of intracranial arteries assessment for each observer was excellent. The SNR and CNR were significantly higher in CS‐MRA compared with Con‐MRA (P < 0.001). The definition of ECA of CS‐MRA was significantly better (Z = –4.9, P < 0.001). Data Conclusion CS‐MRA showed significantly higher image quality with less blur, comparable image diagnostic performance of intracranial arteries, and better display of ECA than Con‐MRA. Level of Evidence: 3 Technical Efficacy Stage: 2 J. Magn. Reson. Imaging 2019;50:1843–1851.

Amplification of MYCN is a poor prognostic feature in neuroblastoma (NBL) indicating aggressive disease. We and others have shown BET bromodomain inhibitors (BETi) target MYCN indirectly by downregulating its transcription. Here we sought to identify agents that synergize with BETi and to identify biomarkers of resistance. We previously performed a viability screen of ∼1,900 oncology-focused compounds combined with BET bromodomain inhibitors against MYCN -amplified NBL cell lines. Reanalysis of our screening results prominently identified inhibitors of aurora kinase A (AURKAi) to be highly synergistic with BETi. We confirmed the anti-proliferative effects of several BETi+AURKAi combinations in MYCN -amplified NBL cell lines. Compared to single agents, these combinations cooperated to decrease levels of N-myc. We treated both TP53 -wild type and mutant, MYCN -amplified cell lines with the BETi JQ1 and the AURKAi Alisertib. The combination had improved efficacy in the TP53 -WT context, notably driving apoptosis in both genetic backgrounds. JQ1+Alisertib combination treatment of a MYCN -amplified, TP53 -null or TP53 -restored genetically engineered mouse model of NBL prolonged survival better than either single agent. This was most profound with TP53 restored, with marked tumor shrinkage and apoptosis induction in response to combination JQ1+Alisertib. BETi+AURKAi in MYCN -amplified NBL, particularly in the context of functional TP53 , provided anti-tumor benefits in preclinical models. This combination should be studied more closely in a pediatric clinical trial.

The aim of the present study was to investigate the status of speckle-type POZ (pox virus and zinc finger protein) protein (SPOP) gene located on chromosome 17q21 in ovarian cancer (OC). The present study evaluated a tissue microarray, which contained 90 samples of ovarian cancer and 10 samples of normal ovarian tissue, using fluorescence hybridization (FISH). FISH is a method where a SPOP-specific DNA red fluorescence probe was used for the experimental group and a centromere-specific DNA green fluorescence probe for chromosome 17 was used for the control group. The present study demonstrated that a deletion of the SPOP gene was observed in 52.27% (46/88) of the ovarian cancer tissues, but was not identified in normal ovarian tissues. Simultaneously, monosomy 17 was frequently identified in the ovarian cancer tissues, but not in the normal ovarian tissues. Furthermore, the present data revealed that the ovarian cancer histological subtype and grade were significantly associated with a deletion of the SPOP gene, which was assessed by the appearance of monosomy 17 in the ovarian cancer samples; the deletion of the SPOP gene was observed in a large proportion of serous epithelial ovarian cancer (41/61; 67.21%), particularly in grade 3 (31/37; 83.78%). In conclusion, deletion of the SPOP gene on chromosome 17 in ovarian cancer samples, which results from monosomy 17, indicates that the SPOP gene may serve as a tumor suppressor gene in ovarian cancer.

Objective. Cone-beam CT (CBCT) in modern pre-clinical small-animal radiation research platforms provides volumetric images for image guidance and experiment planning purposes. In this work, we implemented multi-energy element-resolved (MEER) CBCT using three scans with different kVps on a SmART platform (Precision x-ray Inc.) to determine images of relative electron density (rED) and elemental composition (EC) that are needed for Monte Carlo-based radiation dose calculation. Approach. We performed comprehensive calibration tasks to achieve sufficient accuracy for this quantitative imaging purpose. For geometry calibration, we scanned a ball bearing phantom and used an analytical method together with an optimization approach to derive gantry angle specific geometry parameters. Intensity calibration and correction included the corrections for detector lag, glare, and beam hardening. The corrected CBCT projection images acquired at 30, 40, and 60 kVp in multiple scans were used to reconstruct CBCT images using the Feldkamp–Davis–Kress reconstruction algorithm. After that, an optimization problem was solved to determine images of rED and EC. We demonstrated the effectiveness of our CBCT calibration steps by showing improvements in image quality and successful material decomposition in cases with a small animal CT calibration phantom and a plastinated mouse phantom. Main results. It was found that artifacts induced by geometry inaccuracy, detector lag, glare, and beam hardening were visually reduced. CT number mean errors were reduced from 19% to 5%. In the CT calibration phantom case, median errors in H, O, and Ca fractions for all the inserts were below 1%, 2%, and 4% respectively, and median error in rED was less than 5%. Compared to the standard approach deriving material type and rED via CT number conversion, our approach improved Monte Carlo simulation-based dose calculation accuracy in bone regions. Mean dose error was reduced from 47.5% to 10.9%. Significance. The MEER-CBCT implemented on an existing CBCT system of a small animal irradiation platform achieved accurate material decomposition and significantly improved Monte Carlo dose calculation accuracy.